Temsirolimus: severe hypersensitivity reactions during infusion

Severe infusion-related hypersensitivity reactions have occurred in patients receiving temsirolimus.

From:
Medicines and Healthcare products Regulatory Agency
Published
11 December 2014
Therapeutic area:
Cancer

Article date: January 2009

Temsirolimus (Torisel▼) is an antineoplastic agent used to treat patients with advanced renal-cell carcinoma who have at least 3 of 6 prognostic risk factors (see section 5.1 of the summary of product Characteristics for prognostic factors).

Infusion-related hypersensitivity reactions have occurred during the administration of temsirolimus. The reactions include, but are not limited to, flushing, chest pain, dyspnoea, hypotension, apnoea, loss of consciousness, and anaphylaxis. Up to 3 April, 2008, the marketing authorisation holder for Torisel had received 46 spontaneous reports of infusion-related hypersensitivity reactions, 1 of which had a fatal outcome. Patients must be closely monitored throughout infusion, and appropriate supportive care should be available

In a pivotal clinical trial[footnote 1] in renal-cell cancer, 18 (9%) of 208 of patients treated with temsirolimus experienced allergic reactions of any severity. In all clinical trials to date, about 1% of patients treated with temsirolimus have experienced serious hypersensitivity or infusion reactions.

Most reactions have occurred with the first infusion, commonly within the first few minutes of the start of the infusion; however, reactions with subsequent infusions have also been reported. In some cases, the reactions occurred despite patients having received antihistamine premedication.

Advice for healthcare professionals explains:

  • refer to the summary of product characteristics instructions for premedication of patients, and for dilution and administration of temsirolimus
  • patients should receive 25–50 mg diphenhydramine intravenously (or similar antihistamine) approximately 30 min before the start of every dose of temsirolimus
  • patients must be closely monitored throughout infusion, and appropriate supportive care should be available
  • temsirolimus infusion should be interrupted in all patients who have severe infusion reactions and appropriate medical care given - the patient should be observed for at least 60 min
  • temsirolimus therapy should only be resumed in patients who experience severe or life-threatening reactions after a careful consideration of risks and benefits for the individual
  • if infusion is to be resumed, diphenhydramine (or similar antihistamine) and an H2-receptor antagonist (20 mg famotidine intravenously or 50 mg ranitidine intravenously) should be administered approximately 30 min before restarting temsirolimus infusion - administration of corticosteroids may be considered; however, the efficacy of corticosteroid treatment in this setting has not been established - infusion may then be resumed at a slower rate (up to 60 min) and should be completed within 6 h from the time that temsirolimus is first added to sodium chloride 9 mg/mL (0·9%) solution for injection

  Aritcle citation: Drug Safety Update Januray 2009, vol 2 issue 6: 3.

  1. Hudes G, et al. N Engl J Med 2007; 356: 2271–81 ↩

Published 11 December 2014